Studies in both humans and animals suggest that energy intake and expenditure is modulated both by homeostatic regulatory mechanisms and by non-regulatory processes activated by food-related environmental cues. Through associative learning, such cues have been shown to acquire motivational properties that endow them with the ability to increase food intake even under conditions of satiety (cue-potentiated eating). Furthermore, as a result of other aspects of motivational learning, environmental cues for food may influence intake indirectly, by altering food procurement behavior. For example, these cues may shape and maintain instrumental foraging behaviors (conditioned reinforcement), enhance the performance of other learned behaviors (Pavlovian-to-instrumental transfer;PIT), and guide behavior appropriately after reductions in the value of food (reinforcer devaluation). Although at present little is known about the interaction between such acquired motivational functions of environmental cues and homeostatic regulatory signals, that interaction may contribute to overeating and consequent obesity. Notably, the orexigenic neuropeptide melanin concentrating hormone (MCH) is strongly expressed not only in brain regions directly involved in feeding (e.g., lateral hypothalamus) but also throughout cortico-striatal reward circuitry known to be critical to the display of these learned motivational functions. This distribution of MCH expression suggests that this hormone may serve as an important mediator between metabolic regulatory mechanisms and non-regulatory motivational learning systems. The research proposed here would develop a platform for the study of ingestive behavior and overeating in mice. Specifically, it would use genetic and intracranial pharmacological approaches to explore the roles of MCH in the interaction of regulatory mechanisms and non-regulatory motivational controls over food intake (Aim1) and food procurement (Aim 2) in mouse models. PUBLIC HEALTH RELEVANCE: Emerging evidence suggests that consumption of food and overeating can be driven by both regulatory (i.e., metabolic signals) and non-regulatory factors (i.e., food-related environmental cues). It is possible that the obesity epidemic, whereby individuals'are failing to adapt to modern nutritional challenges, reflects an interaction between regulatory and non-regulatory factors. The melanin concentrating hormone (due to its expression in the brain) may function to mediate between these factors. We will study this in mouse models using genetic and pharmacological approaches.